AAV-based gene delivery of antimicrobial peptides to combat drug-resistant pathogens

Antimicrobial peptides (AMPs) have emerged as potential alternatives to conventional antibiotics due to their novelty and multiple mechanisms of action. Because they are peptides, AMPs are amenable to bioengineering and suitable for cloning and expression at large production scales. However, the efficient delivery of AMPs is an unaddressed issue, particularly due to their large size, possible toxicities, and the development of adverse immune responses. Here, we have reviewed the possibilities of adeno-associated virus (AAV)-based localized gene delivery of AMPs for the treatment of infectious diseases with a special focus on respiratory infections. By discussing the gene delivery mechanism of AAV and the accompanying technical and therapeutic challenges with AMPs, we describe a foundation that emphasizes the use of viral vector-based gene delivery of AMPs for disease treatment.